Neuroinflammation associated with ultrasound-mediated permeabilization of the blood-brain barrier

Olive Jung; Alec Thomas; Scott R Burks; Michael L Dustin; Joseph A Frank; Marc Ferrer; Eleanor Stride

doi:10.1016/j.tins.2022.03.003

Neuroinflammation associated with ultrasound-mediated permeabilization of the blood-brain barrier

Trends Neurosci. 2022 Jun;45(6):459-470. doi: 10.1016/j.tins.2022.03.003. Epub 2022 Apr 20.

Authors

Olive Jung¹, Alec Thomas², Scott R Burks³, Michael L Dustin⁴, Joseph A Frank⁵, Marc Ferrer⁶, Eleanor Stride⁷

Affiliations

¹ Biomedical Ultrasonics, Biotherapy, and Biopharmaceuticals Laboratory, Institute of Biomedical Engineering, University of Oxford, Oxford, UK; 3D Tissue Bioprinting Laboratory, Department of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA.
² Biomedical Ultrasonics, Biotherapy, and Biopharmaceuticals Laboratory, Institute of Biomedical Engineering, University of Oxford, Oxford, UK.
³ The Frank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA.
⁴ Nuffield Department of Orthopedics, Rheumatology, and Musculoskeletal Sciences, Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
⁵ The Frank Laboratory, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, USA; Intramural Research Program, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, Bethesda, MD, USA.
⁶ 3D Tissue Bioprinting Laboratory, Department of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, MD, USA.
⁷ Biomedical Ultrasonics, Biotherapy, and Biopharmaceuticals Laboratory, Institute of Biomedical Engineering, University of Oxford, Oxford, UK. Electronic address: eleanor.stride@eng.ox.ac.uk.

Abstract

The blood-brain barrier (BBB) continues to represent one of the most significant challenges for successful drug-based treatments of neurological disease. Mechanical modulation of the BBB using focused ultrasound (FUS) and microbubbles (MBs) has shown considerable promise in enhancing the delivery of therapeutics to the brain, but questions remain regarding possible long-term effects of such forced disruption. This review examines the evidence for inflammation associated with ultrasound-induced BBB disruption and potential strategies for managing such inflammatory effects to improve both the efficacy and safety of therapeutic ultrasound in neurological applications.

Keywords: blood–brain barrier; cavitation; focused ultrasound; immunomodulation; immunoprivilege; microbubbles; neurological disease; neurovasculature; sterile inflammation.

Publication types

Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Biological Transport
Blood-Brain Barrier*
Brain
Humans
Magnetic Resonance Imaging
Microbubbles
Neuroinflammatory Diseases*

Grants and funding

Z99 HG999999/ImNIH/Intramural NIH HHS/United States